The Effects of Topical Corticosteroid Use on Insulin Sensitivity and Bone Turnover

NCT04114097 | Completed Phase 4 DMC

• 1 other identifier: H-18064175
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators believe that the emerging epidemiological evidence connecting topical use of corticosteroids to the development of type 2 diabetes and osteoporosis point to potentially massive, yet clinically unacknowledged problems associated with topical corticosteroid treatment. Using state-of-the-art methodology, the present study will delineate the impact of topical corticosteroid use on insulin sensitivity and bone turnover markers in patients with atopic dermatitis and, thus, provide important data that may have implications for millions of people using topical corticosteroids.

Conditions

Atopic Dermatitis; Atopic Eczema

Keywords

topical corticosteroids; topical calcineurin inhibitors

Outcome Measures

Primary Outcomes (1)

• Change in whole-body insulin sensitivity

  Change in whole-body insulin sensitivity during treatment with topical corticosteroid use compared to the control group treated with topical calcineurin inhibitors. Insulin sensitivity will be assessed by the hyperinsulinaemic euglycaemic clamp method with glucose and glycerol tracer and indirect calorimetry (rate of disappearance (Rd)).

  Baseline, after 14 days daily treatment, and after 4 weeks of twice daily treatment twice weekly

Study Arms (2)

Betamethasone-17-valerat + placebo ointment

EXPERIMENTAL

Atopic dermatitis patients: topical treatment with twice daily full-body ointment containing corticosteroid ("Betnovate", betamethasone dipropionate ointment 0.1%) and placebo

Drug: Betnovate, betamethasone dipropionate ointment 0.1% and placebo

Tacrolimus ointment

ACTIVE COMPARATOR

Atopic dermatitis patients: topical treatment with twice daily full-body ointment containing calcineurin inhibitor ("Protopic", tacrolimus ointment 0.1%)

Drug: Protopic, tacrolimus ointment 0.1%

Interventions

Betnovate, betamethasone dipropionate ointment 0.1% and placebo DRUG

Explore the systemic effects of Betnovate

Betamethasone-17-valerat + placebo ointment

Protopic, tacrolimus ointment 0.1% DRUG

Compare the systemic effects of Betnovate to Protopic

Tacrolimus ointment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-75 years
• AD according to the Hanifin and Rajka Criteria24
• AD for at least 3 years
• BMI ≤ 30 kg/m2
• Haemoglobin A1c (HbA1c) ≤ 42 mmol/mol (6.0%)
• Normal haemoglobin (men: 8.3-10.5 mmol/L and women 7.3-9.5 mmol/L. A 5% deviation will be allowed if the patient besides this is healthy)
• Informed consent
• In general patients should not be diagnosed with diseases that may affect or be affected by the study/treatment (evaluated by a doctor) (such as untreated skin infections, acne vulgaris (beside face region), a skin barrier defect, such as Netherton's syndrome, lamellar ichthyosis, generalized erythroderma or cutaneous Graft Versus Host Disease, congenital or acquired immunodeficiencies or in patients on therapy that cause immunosuppression, and Protopic ointment should not be applied to lesions that are considered to be potentially malignant or pre-malignant. Further patients should not suffer from kidney or liver disease/insufficiency. See the SPC for Protopic and Betnovate.)

You may not qualify if:

• Diagnosed diabetes mellitus
• Other chronic inflammatory diseases (including but not limited to rheumatoid arthritis, inflammatory bowel disease etc) beside AD and non-treatment demanding rhinitis or asthma (treated within the last 4 weeks)
• Pregnancy (a urine test will be done at every visit and birth control is required, see below\*)
• Breast feeding
• Treatment with drugs that might affect the glucose metabolism beside TCS within a month prior to the project
• Daily smoker, alcoholic, or drug abuser
• Hypersensitivity to Protopic or Betnovate

Sponsors & Collaborators

• Jacob Thyssen: lead
• LEO Pharma: collaborator

Study Sites (1)

Department of Dermatology and Allergy

Hellerup, Capital Region, 2900, Denmark

Location

Related Publications (1)

• Gether L, Storgaard H, Kezic S, Jakasa I, Hartmann B, Skov-Jeppesen K, Holst JJ, Pedersen AJ, Forman J, van Hall G, Sorensen OE, Skov L, Ropke MA, Knop FK, Thyssen JP. Effects of topical corticosteroid versus tacrolimus on insulin sensitivity and bone homeostasis in adults with atopic dermatitis-A randomized controlled study. Allergy. 2023 Jul;78(7):1964-1979. doi: 10.1111/all.15690. Epub 2023 Mar 21.

  PMID: 36824052 DERIVED

MeSH Terms

Conditions

Dermatitis, Atopic

Interventions

Betamethasone Valerate; Tacrolimus

Condition Hierarchy (Ancestors)

Skin Diseases, Genetic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Eczematous; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Betamethasone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Macrolides; Lactones; Organic Chemicals

Study Officials

• Jacob P Thyssen, Professor, MD, DMSc

  Department of Dermatology and Allergy, Gentofte Hospital, Denmark

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, consultant

Model Details: randomised, two-arm, active comparator, double-dummy, double-blinded trial

Study Record Dates

• First Submitted: October 1, 2019
• First Posted: October 3, 2019
• Study Start: August 22, 2019
• Primary Completion: March 15, 2021
• Study Completion: March 15, 2021
• Last Updated: April 28, 2021

Record last verified: 2021-04

Locations

DK (1)